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Right Bundle branch block7

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RBBB does not afect the cardiac axis.

First line antihypertensives

[!TIP] AACT - A2CT => A square CT !

• ACEi
• ARB
• CCB - DHP or nDHP
• Thiazide or thiazide like diuretic ([[Electrolyte balance#^7b5c73|thiazide action]])

Primary prevention of atherosclerotic cardiovascular disease (ASCVD)

#2021GM-NOV Q18

How is risk calculated?

There are many risk calculators, some region specific. ? Different guideline use different calculators.

Who needs primary prevention?

Consists of statin therapy and possibly aspirin.

Statin therapy

Always given in addition to non pharmacologic measures.

Cutoffs for statin therapy:

• If LDL-C is > 190 mg/dL or 4.9 mmol/L
  • Evaluate for familial hypercholesterolaemia -> treat if present.
  • If no familiar hypercholesterolaemia -> treat with statin.
• If LDL-C < 190 mg/dL or 4.0 mmol/L
  • If Risk > 20%, start with high dose statin therapy. If not, moderate doses of statin.
  • Treat with statin if 10 year risk > 10% (considered high risk)
  • Risk 5-10% -> discuss with patient
  • Risk < 5% -> No need of statin therapy.

Source
These cutoff's are 'consistent with many guidelines' - Source
LDL-C levels should be repeated 6 weeks after initiation of therapy.

[!INFO] Lipid lowering drugs which show no benefit
clofibrate , cholestyramine, or gemfibrozil did not show benefits for these medications on coronary mortality

Source

Aspirin therapy

Benefits of protection Vs. Risk of bleeding is closely matched. (In those without previous ASCVD, Aspirin decreases ASCVD risk but increases bleeding risk).
Needs to be decided on case by case basis along with patient choice.

[[statinIntensity.png]] <- effectiveness of cholesterol lowering drugs

Ezetemibe

Novel class of lipid lowering drug.
Blocks intestinal absorption of cholesterol by blocking NPC1L1 sterol transporter.
Does not inhibit hepatic cholesterol synthesis or reduce biliary excretion of cholesterol.

Ezetimibe causes a reduction in LDL levels of 13-20%.
Can be coadministered with fenofibrate or HMG-CoA reductase inhibitors, but the recommendation is to dose it at least 2 hours before or 4 hours after taking bile acid sequestrants.

Pupillary reflex arc

Pupil size is maintained by a balance between sympathetic and parasympathetic tone.

• parasympathetic:
  • causes constriction; begins at the Edinger-Westphal nucleus near the occulomotor nerve nucleus. The fibers enter the orbit with CNIII nerve fibers and ultimately synapse at the cilliary ganglion.
• sympathetic:
  • causes dilation - mydriasis
  • Sympathetic innervation begins at the cortex with the first synapse at the cilliospinal center ( Budge's center ). Post synaptic neurons travel down all the way through the brain stem and finally exit through the cervical sympathetic chain and the superior cervical ganglion. They synapse at the superior cervical ganglion where third-order neurons travel through the carotid plexus and enter into the orbit through the first division of the trigeminal nerve.
    
    Note: ciliary ganglion is mislabeled
    Source

The short ciliary nerve is what carries the post ganglionic parasympathetic neurons.

Location of the parasympathetic fibers

Isolated oculomotor nerve palsy with pupillary involvement in adults is usually related to compression of the third nerve either by an intracranial aneurysm,typically originating at the junction of the posterior communicating and the internal carotid arteries, or by a pituitary tumor (such as in pituitary apoplexy). Both disorders are life-threatening conditions.
[!INFO] Pressure affects the Parasympathetic nerves

Risk factors for delirium

• Advanced age
• underlying CNS disease : dementia, Parkinson etc.
• multiple medications
• frailty, malnutrition
• untreated pain
• bladder catheterization
• limb fractures
• poor eyesight and hearing
• sleep deprivation
• organ failure
• dehydration!

Prevention of delirium

• orientation
• cognitive stimulation: family visits
• facilitation of normal sleep
• early mobilization
• seeing and hearing aids
• pain management
• medications have not been proven to be effective in preventing delirium.
• low dose haloperidol can be used to treat aggressive patients.

Drugs:

• specially benzodiazepines
• analgesics : even NSAIDS
• Any psychoactive drug
• any drug acting on the CNS like antiarrhythmics and beta blockers
• antibiotics..
• so basically any drug

Hypoactive delirium

• Hypoactive presentations of delirium are more common than the classically agitated, hyperactive forms and may be overlooked

Osteoarthritis (OA)

[!INFO] OA isn't just wear and tear
OA is not simply a disease of wear and tear.
Cartilage destruction is a central event but there is definite inflammatory and genetic predisposition as evidenced the identified risk factors and joint prevalence.

Pathogenesis:

OA is considered a disease of the joint, as a whole organ.
Destruction of articular cartilage is a central feature. However, all other joint tissues are affected. (ligaments, tendone, synovium, menisci, subchondral bone, capsule).
Joint cells produce proinflammatory mediates (probably IL-1, IL-6 and TNF) which also stimulate the action of proteases (matrix metalloproteinases MMP) that mediate extracellular matrix destruction.

Sub chondral bone becomes sclerotic (after exposure from destruction of overlying cartilate)

There is a spectrum of disease from

1. cartilage destruction with normal bone
2. cartilage destruction with massive new bone formation at joint margins.

Risk factors:

1. Age
2. Joint injury - called 'post traumatic OA'. Changes develop within 10 years of injury.
3. Obesity - but not only in weight bearing joints! (Increases OA risk in hand as well)
   1. Could be due to adipose tissue macrophages producing cytokines.
4. Mechanical factors: joint shape etc. (bow legs, knock knee), hypermobility,
5. Female sex. (OA of hands and knees is commoner in Women but OA of hip is equally prevalent)
   1. mnemonic: "He Held His Hip in Pain"
   2. Knee OA is more common in asians
   3. OA may flare after menopause.
6. Genetics : some inherited forms of OA produce OA as early as adolescence. OA in general is thought to have a strong hereditary component.
7. There is an inverse relationship between OA and osteoporosis
8. Activities: certain sports and professions (mining, farming) increase risk of OA.
9. Systemic diseases: [[Genetics Notes#Haemochromatosis|Haemochromatosis]], Acromegaly, Sickle cell disease, recurrent haemarthrosis in haemophilia.

Subtypes of OA

Main categories are localized and generalized:

Localized OA

Nodal OA

Initially soft tissue swelling with signs of inflammation.
Several joints will be affected sequentially.
Over years, inflammation settles leaving behind bony nodules on the posterolateral aspect of interphalangeal joints.
DIP more frequently involved than PIP.

Familial
Typical pattern of polyarticular involvement of the hand joints.
Female predomimance, develops around menopause.
Associated with nodal generalized OA (i.e knee, hip, spine OA)
Limited functional impairement.
Fixed adduction of the thumb (squared hand) can occur with OA of the thumb.

Investigations

Imaging:

Radiological OA may not be symptomatic and may not progress.

Treatment:

There are no medical treatments proven to halt or reverse OA.

Weber syndrome

Caused by ischemia of the posterior cerebral artery.

• CNIII palsy with
• contralateral hemiplegia
• contralateral parkinsonian rigidity.

(search: jugular venous pressure)

C wave - (?isovolumic) ventricular contraction
X descent - atrial relaxation
Y descent - opening of tricuspid valve. (trycuspid)
Veins which collapse with inspiration suggest a normal JVP. If they don't collapse, JVP is elevated. Source

[!INFO] Kussmaul's sign
Kussmaul's sign: neck veins rise in inspiration rather than fall—often a sign of pericardial tamponade or right heart failure (acute right ventricular myocardial infarction)

[!INFO] Fridrick's sign
Friedrich's sign: exaggerated "x" wave or diastolic collapse of the neck veins from constrictive pericarditis.
Some sources say it's the Y descent that's exagerrated.
Source

[!WARNING] Tricuspid regurgitation
TR causes an elevated V wave!: not an elevated C wave like you would expect.
Source
Source

See also

Source
Neprilysin (AKA neutral endopeptidase, NEP) degrades some peptides helpful in heart failure (like ANP, bradykinin etc) and also degrades angiotensin II (which is harmful).

Inhibition of neprilysin is a double edged sword because it causes accumulation of beneficial BNP + others but also deleterious angiotensin II.

Therefore, neprilysin inhibitor is always given together with an angiotensin receptor blocker to minimize the effects of the accumulated angiotensin.
An ACE inhibitor cannot be used instead of the ARB because ACEi and Neprilysin inhibitors both increase bradykinin which can cause angioedema.
Eg: Sacubitril valsartan. (sacubitril is a pro drug

Bradykinin

• A peptide with a half life of 17 seconds!.
• Increases capillary permeability; potent vasodilator. -> accumulation causes angiooedema and possibly the dry cough of ACEi therapy.
• Broken down by ACE and neprilysin.

BNP - secreted by ventricles

• Can be normal in HF with preserved EF #2021GM-NOV Q14